Vertebral fractures are the most common fracture in older adults, occurring in 20-35% of women and 15-25% of men over the age of 50, and are associated with significant morbidity, increased mortality, and annual costs exceeding $1 billion in the United States. However, outside of low bone strength due to osteoporosis, there is limited understanding of the factors that cause vertebral fractures, hindering our ability to predict and prevent these injuries. An unexplained observation is that vertebral fractures occur more often in some locations, specifically mid-thoracic (T7-T8) and thoraco-lumbar (T12-L1) vertebrae, than others. It has been suggested that biomechanical factors predispose these areas to fracture by increasing vertebral loading, but these ideas remain largely unexplored. Based on our preliminary data, we hypothesize that the biomechanical effects of the rib cage and increased thoracic kyphosis (spinal curvature) result in greater vertebral loading in the mid- thoracic and thoraco-lumbar spinal regions, respectively. Age-related changes in these factors may thus increase the risk of age-related vertebral fractures in these regions. In this project, we will examine how the rib cage, rib cage stiffness and thoracic kyphosis affect vertebral loading. First we will conduct an in vitro mechanical testing study of cadaveric thoracic spine specimens to determine the effects of the rib cage on vertebral loading, and whether a stiffer rib cage increases vertebral loading in the mid-thoracic spine. Second, we will perform an in vivo human subjects study to determine the association of age and thoracic hyperkyphosis with thoracic range of motion (as a measure of thoracic stiffness). Furthermore, we will determine the influence of thoracic stiffness and kyphosis on estimated vertebral loading, to determine if loading is increased in the mid-thoracic and thoraco-lumbar vertebrae. The data collected in these studies, including in vivo measurements of thoracic vertebral kinematics from an open, upright magnetic resonance imaging device, will be used to develop and validate of a unique musculoskeletal model of the thoracic spine, which will be used to estimate vertebral loading while accounting for the effects of the rib cage and spinal curvature. The broad lack of information on thoracic biomechanics has previously stymied the development and validation of such a model, which will be of great importance in understanding thoracic spine biomechanics. Overall, the knowledge gained and model created in this work will advance the long term goal of better understanding of the causes of vertebral fractures, ultimately leading to improved methods of predicting and preventing vertebral fracture that will improve health and quality of life for millions of older adults. Furthermore, increased knowledge of thoracic biomechanics, and the availability of a well-validated musculoskeletal model of the thoracic spine, will support future research in other areas such as back pain, workplace and traumatic injuries, surgical planning and rehabilitation.